We study sulfur metabolism using skin fibroblasts and have concentrated on the following areas: 1. Discovery and investigation of a mutant mouse which stores cystine in lysosomes as do cystinotic patients. 2. Continued study of the glutathione cycle which when manipulated with inhibitors or stimulators will directly vary the cystine levels in cystinotic cells. 3. Study of the treatment of cystinosis with cysteamine and the resultant discovery that pantethine (a much less toxic compound) will lower cystine levels in cystinotic cells as well as does cysteamine. This includes negotiating for a clinical trial of pantethine. 4. Efforts to define the source of cystinotic cystine by way of the study of metalothionine, a protein that contains one third cysteine residues and was found in 35S-cystine labeled cystinotic cells at levels two fold that found in normal cells. 5. Availability of diagnostic service for detection of cystinosis in new cases and for amniocentesis.